Heterozygous APOE Christchurch in familial Alzheimer’s disease without mutations in other Mendelian genes
Abstract
We present the clinical and neuropathological findings of a patient with early onset Alzheimer's dementia (AD), heterozygous carrier of the rare Apolipoprotein E Christchurch (APOEch) variant. The patient did not harbor any pathogenic mutation in known Mendelian genes related to AD or other neurodegenerative disorders. A sibling of this patient, also carrying the APOEch variant, developed AD at the age of 66 years old. Our data suggest a possible deleterious effect of this variant, which contrast with the protective role that has been previously shown in a subject homozygous for the APOEch with he Paisa PSEN1 mutation.
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To date, few studies have reported on the effect of APOECh due to limited number of carriers in the population.
“To date, few studies have reported on the effect of APOECh due to limited number of carriers in the population [5, 6, 8].”
From Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants (2023) · cites this paper as [6]
The protective effect of the APOE R136S mutation seems to require homozygosis, given that four individuals with PSEN1-E280A and heterozygous for APOEε3R136S developed mild cognitive impairment at the expected age of 45 years and some APOEε3R136S heterozygous individuals with autopsy-proven Alzheimer disease had early onset of symptoms.
“The protective effect of the APOE R136S mutation seems to require homozygosis, given that four individuals with PSEN1-E280A and heterozygous for APOEε3R136S developed mild cognitive impairment at the expected age of 45 years36 and some APOEε3R136S heterozygous individuals with autopsy-proven AD had early onset of symptoms40.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [40]
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Multifaceted roles of APOE in Alzheimer disease
Jackson, R. J., Hyman, B. T., & Serrano-Pozo, A. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-00988-2 · Cited by 193 · see citing works
Characterization of APOE Christchurch carriers in 455,306 UK Biobank participants
He, K. Y., Khramtsova, E. A., Cabrera-Socorro, A., Zhang, Y., Li, S., Sarver, B. A. J., Smets, B., Li, Q. S., De Muynck, L., Parrado, A. R., et al. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00684-7 · Cited by 8 · see citing works
- Authors
- Hernandez, I., Gelpi, E., Molina‐Porcel, L., Bernal, S., Rodríguez‐Santiago, B., Dols‐Icardo, O., Ruiz, A., Alcolea, D., Boada, M., Lleó, A., & Clarimón, J.
- Affiliations
- Instituto de Salud Carlos III (ES)
- Division of Neuropathology and Neurochemistry Department of Neurology Medical University of Vienna Vienna Austria
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Hospital de Sant Pau (ES)
- Universitat Autònoma de Barcelona (ES)
- Research Center and Memory Clinic Fundació ACE Institut Català de Neurociències Aplicades Universitat Internacional de Catalunya Barcelona Spain
- Corresponding author
- Clarimón, Jordi
- ORCID
- Venue
- Neuropathology and Applied Neurobiology
- Publisher
- Wiley
- Published
- 2020-11-05
- Volume
- 47
- Issue
- 4
- Pages
- 579-582
- ISSN
- 0305-1846 (ISSN-L)
- 1365-2990
- OpenAlex
- W3093715759
- Semantic Scholar
- 1f79d1011b5159854bb15e70d225e1330e7ba86e
- Cited by
- 19
- References
- 8
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 1
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropathology and Applied Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Regional Development Fund
- Generalitat de Catalunya (2017 SGR 00547)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- familial Alzheimer's disease, apolipoprotein E, neuropathology
- MeSH terms
- Aged, Alzheimer Disease, Apolipoproteins E, Brain, Heterozygote, Humans, Male, Mutation, Pedigree
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